The primary emphasis of our research effort has focused on the molecular mechanism of the translational controls which regulate protein synthesis in reticulocyte lysates. This is a highly efficient experimental model for the study of translational events due to (a) the rapid of in vitro protein synthesis, (b) the control of protein synthesis by heme, (c) the absence of transcriptional events, and (d) the reproducibility of the system. Previous studies have demonstrated that in the absence of added heme, protein synthesis in reticulocyte lysates proceeds at a maximal linear rate for several minutes and then ceases abruptly. The addition of low levels of heme releases inhibition and restores normal synthesis. The regulatory function of heme appears to be mediated through a translational inhibitor which is formed in heme-depleted lysates; addition of the isolated inhibitor to lysates produces an inhibition analogous to heme-deficiency. Similary kinetics of inhibition are induced by dsRNA and GSSG. Based on several criteria, the four modes of inhibition appear to have similar inhibitory mechanisms, which are exerted at an early step in protein chain initiation. Purification of the translational inhibitor enabled us to examine a broad range of the parameters of inhibition. Preliminary findings may be summarized as follows: (1) The initiation factor (IF) which mediates the binding of initiator Met-tRNAf to the 40S subunit, is capable of reversing all four modes of inhibition; during the onset of inhibition, the available pool of IF appears to be depleted or masked until the inhibition is released. (2) Cyclic AMP also reverses all four types of inhibition; this effect led to the finding that a cAMP-dependent protein kinase is associated with the purified inhibitor, and appears to be linked to the inhibitory function. In addition to these studies, we have obtained preliminary evidence for the presence of similar translational inhibitors in non-erythroid cells including Krebs ascites tumor cells, Ehrlich ascites tumor cells, and rat liver. All of these findings are under further investigation. In addition, the nature of the dsRNA-induced inhibitor is being examined to determine if a protein kinase activity is also involved in this inhibition. In a related study a major effort has been initiated to examine the structure and function of the erythroid plasma membrane during erythroid (Text Truncated - Exceeds Capacity)